We propose to identify unusual types of electrical activity in the human brain that lead to seizures. Epilepsy, a tendency toward recurrent seizures, affects 0.5% of the population. While many patients with epilepsy respond to medication, 10% are medically refractory. If the source of seizures can be localized in the brain (the epileptogenic zone, EZ), surgical removal of that tissue may be possible. In straightforward cases, 80% of patients become seizure-free after such surgery, leading to significant improvements in quality-of-life. However, localizing the EZ is challenging. When traditional techniques fail, subdural electrodes may be surgically implanted to find the seizure onset or interictal spikes. In these cases, only 50% of patients receiving subsequent surgery become seizure-free. To improve EZ localization and surgical outcomes for these patients, we propose studying high-frequency low-voltage activity (HFLV), instead of the current practice of localizing interictal spikes. HFLV is a type of electrical cortical activity that has recently been associated with the EZ, both interictally and at seizure onset. While others have detected HFLV using surgically implanted subdural electrodes (electrocorticography, ECoG), we will attempt to identify HFLV using noninvasive methods. Specifically, we will use the magnetoencephalogram (MEG), which detects extracranial magnetic fields produced by neuronal current flow. In the retrospective phase of our study, we will identify HFLV in archived ECoG and MEG recordings, and determine the spatial concordance between these methods. We will then determine if removal of HFLV- associated tissue in subsequent surgery correlated with seizure freedom. We will thereby determine whether MEG is an adequate noninvasive alternative to ECoG for HFLV identification, and also validate HFLV's clinical importance. In the prospective phase, we will use MEG and ECoG systematically in patients eligible for epilepsy surgery, and determine which HFLV frequency bands (subtypes) best correlate with the epileptogenic zone. We will also study surgical outcomes and pathology of resected tissue in this prospective phase, to better understand the importance of HFLV. We believe completion of this project will advance the scientific understanding of epileptogenesis, and more importantly, improve the efficacy of epilepsy surgery for patients with this disease. PUBLIC HEALTH RELEVANCE: Localizing brain tissue responsible for seizures is challenging, but can lead to surgery that may reduce - or even eliminate - seizures for patients with epilepsy. To help identify this tissue, we will study high- frequency low-voltage electrical activity in the brain, whose importance in generating seizures was only recently recognized. We will use invasive (electrocorticography) and noninvasive (magnetoencephalography) techniques to identify this activity, and determine if its presence and location impacts the success of epilepsy surgeries.